study of amg 509 in participants with metastatic castration-resistant prostate cancer

Conditions: Prostate Cancer

Summary: evaluate the safety and tolerability of amg 509 in adult participants and determine the maximum tolerated dose (mtd) or recommended phase 2 dose (rp2d). part 2 is now closed to accrual.


Eligibility criteria:
inclusion criteria: * parts 1, 2, and 5: participants with histologically or cytologically confirmed metastatic castration-resistant prostate cancer (mcrpc) who are refractory to a novel antiandrogen therapy (abiraterone acetate and/or enzalutamide, apalutamide, or darolutamide) and have failed at least 1 (but not more than 2) taxane regimens including for metastatic hormone-sensitive prostate cancer (mhspc) (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). note: a taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. any nht that has been administered and has been stopped for reasons other than progression will not be counted as an additional line of treatment. 1. dose exploration phase: novel antiandrogen therapy must have been given for treatment of metastatic disease. 2. dose expansion phase: participants must not have had more than 2 nhts and 2 taxane regimens in any setting, and an additional up to 2 other systemic anti-cancer treatments are allowed (eg, anti-pd1, parp inhibitors, radioligand therapies, sipuleucel-t, experimental agents) note: combinations are considered one systemic anti-cancer treatment. * part 3: participants with histologically or cytologically confirmed mcrpc who have received no or 1-2 prior nhts (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) given in any disease setting and who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen (unless taxane treatment was administered in hspc setting). 0 1 prior parp inhibitors or sipuleucel t treatments are acceptable. subjects who received prior investigational therapy for the treatment of metastatic disease are not eligible. * parts 4a and 4b: 1. participants with histologically or cytologically confirmed mcrpc who have received no or 1-2 prior nhts (given in any disease setting depending on the part), and no or 1 taxane regimen (for hspc). 2. dose-expansion phase: at least 1 prior nht must have been given; 0-1 prior parp inhibitors are acceptable. 3. 4a: participants planning to receive abiraterone acetate for the first time (participants who received prior abiraterone acetate are not eligible). participants may have had exposure to up to 2 nhts with a similar mechanism of action (apalutamide, enzalutamide or darolutamide) in the non-mcrpc and mcrpc setting. * dose expansion phase: up to approximately 10 subjects with prior exposure to abiraterone acetate may be enrolled into part 4a expansion cohort. d. 4b: participants planning to receive enzalutamide for the first time (participants who received prior enzalutamide/apalutamide or daralutamide are not eligible). * all parts: * participants must have undergone bilateral orchiectomy or be on continuous androgen-deprivation therapy with a gonadotropin releasing hormone (gnrh) agonist or antagonist. * total serum testosterone \<= 50 ng/dl or 1.7 nmol/l. * evidence of progressive disease, defined as 1 or more prostate cancer working group 3 (pcwg3) criteria: 1. psa level \>= 1 ng/ml that has increased on at least 2 successive occasions at least 1 week apart. 2. nodal or visceral progression as defined by response evaluation criteria in solid tumors (recist) 1.1 with pcgw3 modifications. 3. appearance of 2 or more new lesions in bone scan. * eastern cooperative oncology group performance status of 0-1. * adequate organ function, defined as follows: 1. hematological function: 1. absolute neutrophil count \>= 1 x 10\^9/l (without growth factor support within 7 days from screening assessment). 2. platelet count \>= 75 x 10\^9/l (without platelet transfusion within 7 days from screening assessment). 3. hemoglobin \>= 9 g/dl (90 g/l) (without blood transfusion within 7 days from screening assessment). 2. renal function: 1. estimated glomerular filtration rate based on modification of diet in renal disease calculation \>= 30 ml/min/1.73 m\^2. 3. hepatic function: 1. aspartate aminotransferase (ast) and alanine aminotransferase (alt) \< 3 x upper limit of normal (uln) (or \< 5 x uln for participants with liver involvement). 2. total bilirubin (tbl) \< 1.5 x uln (or \< 2 x uln for participants with liver metastases). 4. cardiac function: 1. left ventricular ejection fraction \> 50% (2-d transthoracic echocardiogram \[echo\] is the preferred method of evaluation; multi-gated acquisition scan is acceptable if echo is not available). 2. baseline electrocardiogram (ecg) qtcf \<= 470 msec (average of triplicate values). part 3-retreatment group: * deriving benefit from initial treatment with amg 509 as evidenced by one of the following: 1. confirmed psa50 response. 2. radiographic stable disease/partial response/complete response during 6 cycles of initial treatment with amg 509 and without progression during the first 6 cycles. * no discontinuation for toxicity during the initial treatment with 6 cycles of amg 509. * progressive disease as defined in i106 within 12 months of final dose in their initial treatment with 6 cycles (eot_1). * willingness to have a fresh tumor biopsy prior to initiating the additional course of treatment, depending on safety and feasibility as assessed by investigator. exclusion criteria: * pathological finding consistent with pure small cell, neuroendocrine carcinoma of the prostate or any other histology different from adenocarcinoma. * radiation therapy within 4 weeks of first dose (or local or focal radiotherapy within 2 weeks of first dose). * untreated central nervous system (cns) metastases or leptomeningeal disease. participants with a history of treated cns metastases are eligible if there is radiographic evidence of improvement upon the completion of cns-directed therapy and no evidence of interim progression between the completion of cns-directed therapy and the screening radiographic study. * participants with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of investigational product administration. * confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy. * history of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis); for arterial thrombosis within 12 months of amg 509 initiation; for venous thrombosis, 6 months and stable on anti-coagulation. * myocardial infarction and/or symptomatic congestive heart failure (new york heart association \> class ii) within 12 months of first dose of amg 509 with the exception of ischemia or non-st segment elevation myocardial infarction controlled with stent placement and confirmed by a cardiologist more than 6 months prior to first dose of amg 509. * any anti-cancer therapy or immunotherapy within 4 weeks of start of first dose, not including luteinizing hormone-releasing hormone (lhrh)/gnrh analogue (agonist/antagonist). * prior psma radionuclide therapy within 2 months prior to amg 509 unless participant received \ = 30 days prior to enrollment are eligible (exception: part 3 retreatment). * part 3-retreatment only: any anticancer therapy or immunotherapy, not including luteinizing hormone-releasing hormone/gonadotropin releasing hormone (lhrh/gnrh) analogue (agonist/antagonist), and/or bisphosphonate or denosumab regimen after last dose of amg 509 initial course of treatment.

Keywords: amg 509 mcrpc metastatic castration-resistant prostate cancer prostate cancer psma steap1 steap1 targeted therapy solid tumor immunotherapy immuno-oncology immunooncology bispecific t-cell engager® bite® xmab®